Shih Chuen-Ming, Chen Kwunmin, Wang Yu-Chieh, Lee Pei-Jung, Wang Yi-Ching
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, ROC.
Cancer Detect Prev. 2007;31(5):366-70. doi: 10.1016/j.cdp.2007.10.003. Epub 2007 Nov 26.
Clinical and experimental studies suggest that alteration of the expression level of the p53 gene and other damage responsive genes may be associated with chemoresistance in cancer patients.
The present study evaluated the differences of the basal levels of lymphocytic p53 and p21waf1 mRNA expression collected before receiving cisplatin-based chemotherapy between 48 chemo-ineffective lung cancer patients and 39 chemo-effective lung cancer patients using an optimized semi-quantitative multiplex reverse transcriptase-polymerase chain reaction (RT-PCR).
The data indicated that the mean mRNA level of p53 gene in chemo-ineffective patients (0.66) was 26.9% higher than that of the chemo-effective patients (0.52) with statistical significance (P=0.03), and a significantly higher level of p21waf1 mRNA expression in the chemo-ineffective patients (P=0.03) was also observed. In addition, by the multiplex long quantitative PCR analysis, we demonstrated that chemo-ineffective and chemo-effective patients have similar amounts of UV damage on their p53 gene of lymphocyte DNA through equal UV treatment.
Our results suggest that elevated levels of p53/p21waf1 mRNA in blood lymphocytes collected before chemotherapy may predict the chemoresponses of lung cancer patients.
临床和实验研究表明，p53基因及其他损伤反应基因表达水平的改变可能与癌症患者的化疗耐药相关。
本研究采用优化的半定量多重逆转录聚合酶链反应（RT-PCR），评估了48例化疗无效的肺癌患者和39例化疗有效的肺癌患者在接受基于顺铂的化疗前淋巴细胞p53和p21waf1 mRNA表达基础水平的差异。
数据表明，化疗无效患者的p53基因平均mRNA水平（0.66）比化疗有效患者（0.52）高26.9%，具有统计学意义（P=0.03），且化疗无效患者的p21waf1 mRNA表达水平也显著更高（P=0.03）。此外，通过多重长定量PCR分析，我们证明在相同紫外线处理下，化疗无效和化疗有效的患者淋巴细胞DNA的p53基因上的紫外线损伤量相似。
我们的结果表明，化疗前采集的血液淋巴细胞中p53/p21waf1 mRNA水平升高可能预测肺癌患者的化疗反应。
